The ultimate goal of our research and development program in multiple sclerosis (MS) is to develop a novel MS drug that targets CD24, a GPI-anchored surface glycoprotein that serves as a unique and critical checkpoint for MS pathogenesis. During our previous studies supported by the phase I and phase II grants, we produced a fusion protein between the CD24 extracellular domain and the human IgG1 heavy chain Fc region and showed that the fusion protein has a significant effect on the acute EAE clinical score even when applied after the onset of the disease. Moreover, the fusion protein reduced disease severity and reduced the rate of relapses in the relapsing EAE model. Remarkably, the fusion protein has a very long half-life in vivo and showed no toxicity in the mouse model. The potential relevance of the CD24 target in human multiple sclerosis is substantiated by our discoveries that the polymorphism of CD24 is a genetic modifier for the risk and progression of multiple sclerosis. In collaboration with Gala, a division of Cardinal Health, Inc., we have produced cell lines that stably secrete high levels of CD24. A GLP toxicity lot of more than 60 grams of fusion protein has been produced and 140 grams of cGMP grade product was manufactured as well. In the next phase, we will carry out the necessary studies for an investigative new drug (IND) filing with the Food and Drug Administration. At the same time, we will analyze the immunological and non-immunological mechanisms by which CD24Ig works as a therapeutic drug for MS. Our proposed studies will provide data for IND filing and will therefore pave the way for clinical trials of the novel drug. They will mark the most important milestones in a project that has been supported by the SBIR grant, aimed at developing novel therapeutics for MS with implications in other neurological and autoimmune diseases. PUBLICE HEALTH RELEVANCE: The project is proposed to continue our current research and finalize necessary studies for an investigative new drug (IND) filing with the Food and Drug Administration. This will lead us through phase I and phase II clinical trials and toward the development of a novel drug for multiple sclerosis, with implications for other neurological diseases. [unreadable] [unreadable]